Artikel ; Online: Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites.
2019 Band 10, Heft 1, Seite(n) 3950
Abstract: Immunization with attenuated whole Plasmodium sporozoites constitutes a promising vaccination strategy. Compared to replication-deficient parasites, immunization with replication-competent parasites confers better protection and also induces a type I IFN ...
| Abstract | Immunization with attenuated whole Plasmodium sporozoites constitutes a promising vaccination strategy. Compared to replication-deficient parasites, immunization with replication-competent parasites confers better protection and also induces a type I IFN (IFN-1) response, but whether this IFN-1 response has beneficial or adverse effects on vaccine-induced adaptive immunity is not known. Here, we show that IFN-1 signaling-deficient mice immunized with replication-competent sporozoites exhibit superior protection against infection. This correlates with superior CD8 T cell memory including reduced expression of the exhaustion markers PD-1 and LAG-3 on these cells and increased numbers of memory CD8 T cells in the liver. Moreover, the adoptive transfer of memory CD8 T cells from the livers of previously immunized IFN-1 signaling-deficient mice confers greater protection against liver stage parasites. However, the detrimental role of IFN-1 signaling is not CD8 T cell intrinsic. Together, our data demonstrate that liver stage-engendered IFN-1 signaling impairs hepatic CD8 T cell memory via a CD8 T cell-extrinsic mechanism. |
|---|---|
| Mesh-Begriff(e) | Adaptive Immunity/immunology ; Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/parasitology ; Erythrocytes/immunology ; Erythrocytes/parasitology ; Female ; Immunity, Innate/immunology ; Immunization ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Liver/immunology ; Liver/metabolism ; Liver/parasitology ; Malaria/immunology ; Malaria/parasitology ; Malaria/prevention & control ; Malaria Vaccines/administration & dosage ; Malaria Vaccines/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Plasmodium yoelii/immunology ; Plasmodium yoelii/physiology ; Sporozoites/immunology ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology |
| Chemische Substanzen | Interferon Type I ; Malaria Vaccines ; Vaccines, Attenuated |
| Sprache | Englisch |
| Erscheinungsdatum | 2019-09-02 |
| Erscheinungsland | England |
| Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2553671-0 |
| ISSN | 2041-1723 ; 2041-1723 |
| ISSN (online) | 2041-1723 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-019-11819-0 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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